BPH and inflammation: Pharmacological effects of Permixon on histological and molecular inflammatory markers. Results of a double blind pilot clinical assay

Introduction: The role of infiltrating cells (I.C.), commonly observed in the adenoma interstitial tissue, is unknown. We tested the hypothesis that I.C. are related with BPH progression by: phenotypically characterising these cells; quantifying the expression of lymphokines and growth factors; investigating the response to Permixon (P) in a clinical study. Permixon is a Lipido Sterolic Extract of Serenoa repens possessing pharmacological activities and widely used in the treatment of men with BPH. Material and Methods: A multicenter open pilot study of two parallel groups on BPH patients was carried out. They were randomized to receive either oral Permixon (P) 160 mg bid for three months or to be followed for 3 weeks without any treatment before surgery (control group C). Strict inclusion and exclusion criteria were applied to conform homogeneous groups, avoiding interferences of inflammatory drugs or others. Baseline clinical profile was almost identical in both groups in terms of age (65.7 +/- 5.1 vs. 67.1 +/- 5.8 years), IPSS (19.8 +/- 6.1 vs. 19.0 +/- 5.8), prostate volume (64.8 +/- 18.9 vs. 71.5 +/- 29.3 cc), Q(max) (9.6 +/- 3.2 vs. 10.6 +/- 2.6 ml/s), and Q(L) (4.0 +/- 1.1 vs. 3.5 +/- 0.7). Surgery was ultimately performed on 29 patients (17C, 12P) by TURP or retropubic adenomectomy. Adenoma samples were routinely stained with HE and later prepared for immunohistochemical studies using CD3, CD20 and CD68 antibodies. Counting of positives cells, lymphoid aggregates and foci were done using EnVision technique and the Tech Mate processor. Cytokines, growth factors and eicosanoids were determined by Elisa kits following the manufactured recommendation. Results: Histological: A difference was observed in the number of lymphocytes B between C (91.4 +/- 44.1) and P treated (58.2 +/- 53.7) groups (p = 0.097). Biological markers: TNFalpha and IL-1beta were dramatically lower in the Permixon treated group. Other parameters did not show significant changes. Clinical: IPSS in the Permixon treated group was significantly reduced (p < 0.006) from 20.0 + 5.9 to 14.9 + 3.8 after three months of treatment. Comments: The BPH inflammatory hypothesis was tested in humans. Our pilot study shows a significant reduction of some inflammatory parameters in prostatic tissues of patients treated with Permixon. These biological findings justify a pharmacological effect of this drug on the inflammatory status of the adenoma. A correlation with clinical improvement was observed. (C) 2003 Elsevier B.V. All rights reserved.